HypertensionNCT02293096
Pharmacogenetic Prediction of Metoprolol Effectiveness
A study testing metoprolol succinate, Genotyping and CYP2D6 Phenotyping in people with Hypertension, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The investigators will prospectively follow a population of patients with uncontrolled high blood pressure beginning metoprolol succinate therapy to determine the drug effect in an observational clinical trial. The investigators will determine each individual's genotype for both CYP2D6 and Adrenoceptor Beta 1 (ADRB1). Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- metoprolol succinate, Genotyping and CYP2D6 Phenotyping
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 462 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 23 Aug 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects between age >30 years and < 80 years
- Subjects have diagnosis of uncontrolled essential hypertension.
Who cannot join
- end stage liver disease,
- end stage renal disease,
- pregnant females,
- American Society of Anesthesiologists (ASA) classification of >3,
- wards of the state, prisoners,
- decisionally challenged,
Show all 13Show fewer
- HR<60 bpm,
- AV block>240 msec,
- active reactive airway disease,
- illicit drug abuse in the preceding 30 days,
- hypersensitivity to metoprolol or its derivatives
- severe peripheral arterial circulatory disorders.
- Subjects will have a screening physical exam performed by Dr. Monte prior to enrollment in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver; Emergency Department
Aurora, Colorado, 80045
About this study
The investigators will prospectively follow a population of patients with uncontrolled high blood pressure beginning metoprolol succinate therapy to determine the drug effect in an observational clinical trial. The investigators will determine each individual's genotype for both CYP2D6 and Adrenoceptor Beta 1 (ADRB1). Metabolomic markers will be identified to determine if specific metabolites are associated with drug response. The investigators' overall objective is to determine if genetics predicts metoprolol succinate response better than clinical factors such as age, race, body mass index, dose, and medication co-ingestion.
- Conditions
- Hypertension
- Being tested
- metoprolol succinate, Genotyping, CYP2D6 Phenotyping
- Keywords
- Genotype, CYP2D6, ADRB1
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metoprolol succinateDrug
Also called Lopressor
GenotypingGenetic
Also called CYP2D6 genotyping and ADRB1 genotyping
CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. Thus the investigator, the subject, and the outcomes investigator will be blind to the intervention.
CYP2D6 PhenotypingProcedure or surgery
Also called Dextromethorphan probe of CYP2D6
Phenotype can be discordant from what is predicted by genotype due to variability in absorption, hepatic blood flow, drug interaction and drug elimination. These factors can be accounted for by utilizing a phenotyping assay that determines area under the curve of the probe since the probe is affected by the same variables dictating metabolism phenotype of the therapeutic drug. Investigators will be blind to the patient blood pressure outcome for this intervention.
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping | Experimental | The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors.
metoprolol succinate
Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete.
CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention. Receives: Drug: metoprolol succinate; Genetic: Genotyping; Procedure: CYP2D6 Phenotyping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Pressure Decline
Participants with at least a 10% decrease in SBP
Measured: 4-6 weeks status post initiation
Secondary outcomes (3)
Heart Rate Decline
10 % decline from pre-initiation heart rate will considered a HR decline success. Number of of participants with at least 10% decline is reported.
Measured: 4-6 weeks
Adverse Drug Events: CYP2D6 Metabolizer Status
Occurrence of adverse drug events will be captured and stratified by CYP2D6 metabolizer status (Poor Metabolizer (PM), Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Ultra rapid Metabolizer).
Measured: 6 weeks
Adverse Drug Events: ADRB1 Genotype
Occurrence of adverse drug events will be captured and stratified by ADRB1 genotype (strong responder, good responder, non-responder).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study startSep 2014
- Primary completion23 Aug 2017
- Study completion23 Aug 2017
Why it stopped: Study was terminated due to the change in funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 462 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor
- Investigators
- Andrew Monte, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293096
- Sponsor's protocol ID
- 13-3174
- Other IDs
- 1K23GM110516-01
- Status last verified
- Aug 2021
- First submitted
- 13 Nov 2014
- Last updated
- 16 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Brocker CN, Velenosi T, Flaten HK, McWilliams G, McDaniel K, Shelton SK, Saben J, Krausz KW, Gonzalez FJ, Monte AA. Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites. Hum Genomics. 2020 Mar 11;14(1):10. doi: 10.1186/s40246-020-00260-w.
PubMed 32160915
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Prediction of Metoprolol Effectiveness
- ClinicalTrials.gov ID
- NCT02293096
- Acronym / sponsor ID
- 13-3174
- Conditions
- Hypertension
- Keywords
- Genotype, CYP2D6, ADRB1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to the change in funding.
- Enrolment
- 462 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- Sep 2014
- Primary completion
- 23 Aug 2017 (actual)
- Study completion
- 23 Aug 2017 (actual)
- First posted
- 18 Nov 2014 (estimated)
- Results
- Posted 16 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will prospectively follow a population of patients with uncontrolled high blood pressure beginning metoprolol succinate therapy to determine the drug effect in an observational clinical trial. The investigators will determine each individual's genotype for both CYP2D6 and Adrenoceptor Beta 1 (ADRB1). Metabolomic markers will be identified to determine if specific metabolites are associated with drug response. The investigators' overall objective is to determine if genetics predicts metoprolol succinate response better than clinical factors such as age, race, body mass index, dose, and medication co-ingestion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping | Experimental | Drug: metoprolol succinate, Genetic: Genotyping, Procedure: CYP2D6 PhenotypingThe parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects between age >30 years and < 80 years
- Subjects have diagnosis of uncontrolled essential hypertension.
Key exclusion criteria (13 listed)
- end stage liver disease,
- end stage renal disease,
- pregnant females,
- American Society of Anesthesiologists (ASA) classification of >3,
- wards of the state, prisoners,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metoprolol succinateAlso: Lopressor | Drug | Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping |
| GenotypingAlso: CYP2D6 genotyping and ADRB1 genotypingCYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. Thus the investigator, the subject, and the outcomes investigator will be blind to the intervention. | Genetic | Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping |
| CYP2D6 PhenotypingAlso: Dextromethorphan probe of CYP2D6Phenotype can be discordant from what is predicted by genotype due to variability in absorption, hepatic blood flow, drug interaction and drug elimination. These factors can be accounted for by utilizing a phenotyping assay that determines area under the curve of the probe since the probe is affected by the same variables dictating metabolism phenotype of the therapeutic drug. Investigators will be blind to the patient blood pressure outcome for this intervention. | Procedure or surgery | Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping |
Primary outcome
Blood Pressure Decline
Time frame: 4-6 weeks status post initiation
Participants with at least a 10% decrease in SBP
3 secondary outcomes
Heart Rate Decline
Time frame: 4-6 weeks
Adverse Drug Events: CYP2D6 Metabolizer Status
Time frame: 6 weeks
Adverse Drug Events: ADRB1 Genotype
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32160915Brocker CN, Velenosi T, Flaten HK, McWilliams G, McDaniel K, Shelton SK, Saben J, Krausz KW, Gonzalez FJ, Monte AA. Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites. Hum Genomics. 2020 Mar 11;14(1):10. doi: 10.1186/s40246-020-00260-w.
Related trials for Hypertension
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
Recruiting
Implementing AI-based Glaucoma Screening Within Federally Qualified Health Centers
Glaucoma, Ocular Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Monte, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing metoprolol succinate, Genotyping and CYP2D6 Phenotyping in people with Hypertension, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Pressure Decline (time frame: 4-6 weeks status post initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02293096, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021; AzTrials last refreshed its copy on 7 Nov 2026.